Although some gene mutations can predict response to certain targeted therapies, single-gene testing has limits. Multiple important signaling pathways that may be the causes of human malignancy have continuously been discovered and dissected. Pathway and network diagnostic tests are challenging but are clearly on the way. Through this NIH STTR Phase I study, we will develop a hybrid phosphoproteomic platform to differentiate leukemia at the molecular level. The platform features two innovative products recently introduced by us which are based on multi-functionalized water-soluble nanopolymers, allowing for highly selective, sensitive and simple qualitative and quantitative assessment of protein phosphorylation without the use of expensive phosphospecific antibodies. Due to its size and unique properties, it also offers the capability for multiplexed detection of phosphorylation and total protein amount simultaneously. Combined with targeted mass spectrometric analysis, this hybrid platform will be a powerful tool for biomedical research and development, particularly in the field of leukemia treatment, and a potential clinical tool for cancer diagnosis.